I wrote about something similar to this else where, so let me go into some detail about the NMDA receptor (easy to find anywhere, nothing original here besides some concepts I was personally toying with, and I should note it was done on my phone so don't get mad if my grammar is poor):

"The NMDA receptor is an ionotropic receptor that allows for the transfer of electrical signals between neurons in the brain and in the spinal column. For electrical signals to pass, the NMDA receptor must be open. To remain open, an NMDA receptor must bind to glutamate and to glycine. An NMDA receptor that is bound to glycine and glutamate and has an open ion channel is called "activated."

NMDA receptors aren't activated easily. The receptor is blocked by Mg2+ so it needs to have sufficient depolarization. Even if you have Aspartic acid there (or Glutamate), you need Glycine to be there as well. So you need a few things at once to activate the NMDA receptors, the key thing being the depolarization of say an AMPA receptor near by before any of the binding even matters. Test force gets around the issue of Glycine by using Sarcosine.

NMDA receptors have different subunits, and the effects of the subunits upon activation. Basic message to take home is that DAA is likely not going to elicit toxicity (due to A and B noted below) because toxicity most likely only comes from NR2B subunit. But if it DOES elicist neurotoxicity, keep reading on how to address this.

Chemicals that deactivate the NMDA receptor are called antagonists. NMDAR antagonists fall into four categories:

1) Competitive antagonists, which bind to and block the binding site of the neurotransmitter glutamate;
2) Glycine antagonists, which bind to and block the glycine site;
3) Noncompetitive antagonists, which inhibit NMDARs by binding to allosteric sites; and
4) Uncompetitive antagonists, which block the ion channel by binding to a site within it."

We investigated in rat hippocampus neurons whether 4-(aminobutyl)guanidine (agmatine), formed by decarboxylation ofl-arginine by arginine decarboxylase and metabolized to urea and putrescine, can modulate the function ofN-methyl-d-aspartate (NMDA) receptor channels. In cultured hippocampal neurons studied by whole-cell patch clamp, extracellular-applied agmatine produced a voltage- and concentration-dependent block of NMDA but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid nor kainate currents. Analysis of the voltage dependence of the block suggests that agmatine binds at a site located within the NMDA channel pore with a dissociation constant of 952 μM at 0 mV and an electric distance of 0.62. We also tested effects of several agmatine analogs. Arcaine (1,4-butyldiguanidine) also produced a similar voltage-dependent block of the NMDA current, whereas putrescine (1,4-butyldiamine) had little effect, suggesting that the guanidine group of agmatine is the active moiety when blocking the NMDA channel. Moreover, spermine (an endogenous polyamine) potentiated the NMDA current even in the presence of blocker agmatine or arcaine, suggesting that the guanidine-containing compounds agmatine and arcaine interact with the NMDA channel at a binding site different from that of spermine. Our results indicate that in hippocampal neurons agmatine selectively modulates the NMDA subclass of glutamate receptor channels mediated by the interaction between the guanidine group and the channel pore. The results support other data that agmatine may function as an endogenous neurotransmitter/neuromodulator in brain."

Also:

Effect of Agmatine Against Cell Death Induced by NMDA and Glutamate in Neurons and PC12 Cells

"Therefore, it is conceivable that agmatine, coreleased with glutamate, may act to
inhibit the activation of NMDA receptors during conditions leading to higher glutamate
release. Further in vivo studies, measuring the release of agmatine along with
glutamate are required to verify this hypothesis.
In summary, we have provided evidence that agmatine is a neuroprotective
molecule and reduces excitotoxic cell death induced by glutamate or NMDA.

"Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property."

Another thing to keep in mind from the paper I just pasted above:

"Because axons that innervate pyramidal cells are glutamatergic and
pyramidal cells expressNMDAsubclass of glutamate receptors, it has been proposed
that agmatine may be costored and released with glutamate as a counterregulatory
molecule. Electrophysiological studies of cultured hippocampal neurons have also
supported the contention that agmatine selectively inhibitedNMDAchannels (Yang
and Reis, 1999).

While these previous studies suggested a possible regulatory role for agmatine
in normal glutamatergic neurotransmission, agmatine may also play a role in pathological conditions involving higher activation ofNMDAreceptors. Thus, agmatine
is protective against ischemic injury (Gilad, 1996b), spinal cord injury (Fairbanks
et al., 2000; Gilad and Gilad 2000; Yu et al., 2000) and neuropathic pain (Fairbanks
et al., 1998), conditions that arise from higher NMDA receptor activation and are
reversed byNMDAreceptor antagonists. The present study has provided further evidence
that the neuroprotective action of agmatine could be mediated by the blockade
of NMDA receptors."

Anyhow, I wrote a post about this on a different forum concerning DAA and something with a similar concept to Agmatine in terms of neuroprotective methods, Huperzine A.

Some key differences though:

"Agmatine Fails to Inhibit Cell Death Induced by Calcimycin or Staurosporin
To address the question whether the effect of agmatine on cell death is mediated
by nonspecific blockade of cation channels or by inhibiting intracellular protein
kinase pathways, we investigated other nonexcitoxic cell death models. Calcimycin,
a calcium channel opener, caused a significant increase in LDH release in neurons
(4% vs. 11.5%) and PC12 (4% vs. 12%) cells, indicating marked cell death (Fig. 5).
Agmatine (100 ¹M), when incubated with calcimycin, failed to inhibit the elevated
release of LDH.Asimilar result was obtained with staurosporin, which causes apoptotic
cell death by intracellular actions, where LDH release was not inhibited by
agmatine (100 ¹M) in neurons and PC12 cells (Fig. 5)."

What I said about Huperzine A:

"Huperzine A (?100 µM) had no effect on the binding of [3H]glutamate (low- and high-affinity glutamate sites), [3H]MDL 105,519 (NMDA glycine regulatory site), [3H]ifenprodil (NMDA polyamine site) or [3H]CGS 19755 (NMDA antagonist). These are the things we really worry about when we talk about DAA and NMDA receptors.

Therefore, HUP-A most likely attenuates excitatory amino acid toxicity by blocking the NMDA ion channel and subsequent Ca2+ mobilization at or near the PCP and MK-801 ligand sites."

Now that we have all that said, key thing to keep in mind, once the NMDA receptor is activated (takes a few things to be activated), that is it, it will release the neurotransmitter. If glutamate induced NMDA activation is co-activated with Agmatine release, I would assume that taking DAA will also increase endogenous Agmatine release in order to protect you from glutamatergic neurotoxicity. We can sort of thing of Agmatine as acting as a buffer to keep DAA from over exciting NDMA receptors.

We have DAA present (check, so more NMDA activation now with Glycine, Ca+2 current, agonist DAA here), Agmatine doesn't affect Calcium intracellular mechanisms (check, you need the depolarization to stop the Mg+2 from blocking the site), Glycine present (will happen for activation of the receptor, so check). Say the NMDA receptor is now activated, releases Glutamate, blah blah blah, the Agmatine in the product in theory based on what I posted above is also endogenously released, so exogenous application will enhance that regulatory role of Agmatine so that in higher levels of NMDA receptor activation, it will inhibit the receptor from higher glutamate release (so overexcitation leading to potential neurotoxicity) by inhibting the receptor. Basically Agmatine might be able to prevent the neurotoxicity you always hear about when talking about DAA by preventing overexcitation of NMDA receptors/ reversing the levels of activation.

I wrote about something similar to this else where, so let me go into some detail about the NMDA receptor (easy to find anywhere, nothing original here besides some concepts I was personally toying with, and I should note it was done on my phone so don't get mad if my grammar is poor):

"The NMDA receptor is an ionotropic receptor that allows for the transfer of electrical signals between neurons in the brain and in the spinal column. For electrical signals to pass, the NMDA receptor must be open. To remain open, an NMDA receptor must bind to glutamate and to glycine. An NMDA receptor that is bound to glycine and glutamate and has an open ion channel is called "activated."

NMDA receptors aren't activated easily. The receptor is blocked by Mg2+ so it needs to have sufficient depolarization. Even if you have Aspartic acid there (or Glutamate), you need Glycine to be there as well. So you need a few things at once to activate the NMDA receptors, the key thing being the depolarization of say an AMPA receptor near by before any of the binding even matters. Test force gets around the issue of Glycine by using Sarcosine.

NMDA receptors have different subunits, and the effects of the subunits upon activation. Basic message to take home is that DAA is likely not going to elicit toxicity (due to A and B noted below) because toxicity most likely only comes from NR2B subunit. But if it DOES elicist neurotoxicity, keep reading on how to address this.

Chemicals that deactivate the NMDA receptor are called antagonists. NMDAR antagonists fall into four categories:

1) Competitive antagonists, which bind to and block the binding site of the neurotransmitter glutamate;
2) Glycine antagonists, which bind to and block the glycine site;
3) Noncompetitive antagonists, which inhibit NMDARs by binding to allosteric sites; and
4) Uncompetitive antagonists, which block the ion channel by binding to a site within it."

We investigated in rat hippocampus neurons whether 4-(aminobutyl)guanidine (agmatine), formed by decarboxylation ofl-arginine by arginine decarboxylase and metabolized to urea and putrescine, can modulate the function ofN-methyl-d-aspartate (NMDA) receptor channels. In cultured hippocampal neurons studied by whole-cell patch clamp, extracellular-applied agmatine produced a voltage- and concentration-dependent block of NMDA but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid nor kainate currents. Analysis of the voltage dependence of the block suggests that agmatine binds at a site located within the NMDA channel pore with a dissociation constant of 952 μM at 0 mV and an electric distance of 0.62. We also tested effects of several agmatine analogs. Arcaine (1,4-butyldiguanidine) also produced a similar voltage-dependent block of the NMDA current, whereas putrescine (1,4-butyldiamine) had little effect, suggesting that the guanidine group of agmatine is the active moiety when blocking the NMDA channel. Moreover, spermine (an endogenous polyamine) potentiated the NMDA current even in the presence of blocker agmatine or arcaine, suggesting that the guanidine-containing compounds agmatine and arcaine interact with the NMDA channel at a binding site different from that of spermine. Our results indicate that in hippocampal neurons agmatine selectively modulates the NMDA subclass of glutamate receptor channels mediated by the interaction between the guanidine group and the channel pore. The results support other data that agmatine may function as an endogenous neurotransmitter/neuromodulator in brain."

Also:

Effect of Agmatine Against Cell Death Induced by NMDA and Glutamate in Neurons and PC12 Cells

"Therefore, it is conceivable that agmatine, coreleased with glutamate, may act to
inhibit the activation of NMDA receptors during conditions leading to higher glutamate
release. Further in vivo studies, measuring the release of agmatine along with
glutamate are required to verify this hypothesis.
In summary, we have provided evidence that agmatine is a neuroprotective
molecule and reduces excitotoxic cell death induced by glutamate or NMDA.

"Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property."

Another thing to keep in mind from the paper I just pasted above:

"Because axons that innervate pyramidal cells are glutamatergic and
pyramidal cells expressNMDAsubclass of glutamate receptors, it has been proposed
that agmatine may be costored and released with glutamate as a counterregulatory
molecule. Electrophysiological studies of cultured hippocampal neurons have also
supported the contention that agmatine selectively inhibitedNMDAchannels (Yang
and Reis, 1999).

While these previous studies suggested a possible regulatory role for agmatine
in normal glutamatergic neurotransmission, agmatine may also play a role in pathological conditions involving higher activation ofNMDAreceptors. Thus, agmatine
is protective against ischemic injury (Gilad, 1996b), spinal cord injury (Fairbanks
et al., 2000; Gilad and Gilad 2000; Yu et al., 2000) and neuropathic pain (Fairbanks
et al., 1998), conditions that arise from higher NMDA receptor activation and are
reversed byNMDAreceptor antagonists. The present study has provided further evidence
that the neuroprotective action of agmatine could be mediated by the blockade
of NMDA receptors."

Anyhow, I wrote a post about this on a different forum concerning DAA and something with a similar concept to Agmatine in terms of neuroprotective methods, Huperzine A.

Some key differences though:

"Agmatine Fails to Inhibit Cell Death Induced by Calcimycin or Staurosporin
To address the question whether the effect of agmatine on cell death is mediated
by nonspecific blockade of cation channels or by inhibiting intracellular protein
kinase pathways, we investigated other nonexcitoxic cell death models. Calcimycin,
a calcium channel opener, caused a significant increase in LDH release in neurons
(4% vs. 11.5%) and PC12 (4% vs. 12%) cells, indicating marked cell death (Fig. 5).
Agmatine (100 ¹M), when incubated with calcimycin, failed to inhibit the elevated
release of LDH.Asimilar result was obtained with staurosporin, which causes apoptotic
cell death by intracellular actions, where LDH release was not inhibited by
agmatine (100 ¹M) in neurons and PC12 cells (Fig. 5)."

What I said about Huperzine A:

"Huperzine A (?100 µM) had no effect on the binding of [3H]glutamate (low- and high-affinity glutamate sites), [3H]MDL 105,519 (NMDA glycine regulatory site), [3H]ifenprodil (NMDA polyamine site) or [3H]CGS 19755 (NMDA antagonist). These are the things we really worry about when we talk about DAA and NMDA receptors.

Therefore, HUP-A most likely attenuates excitatory amino acid toxicity by blocking the NMDA ion channel and subsequent Ca2+ mobilization at or near the PCP and MK-801 ligand sites."

Now that we have all that said, key thing to keep in mind, once the NMDA receptor is activated (takes a few things to be activated), that is it, it will release the neurotransmitter. If glutamate induced NMDA activation is co-activated with Agmatine release, I would assume that taking DAA will also increase endogenous Agmatine release in order to protect you from glutamatergic neurotoxicity. We can sort of thing of Agmatine as acting as a buffer to keep DAA from over exciting NDMA receptors.

We have DAA present (check, so more NMDA activation now with Glycine, Ca+2 current, agonist DAA here), Agmatine doesn't affect Calcium intracellular mechanisms (check, you need the depolarization to stop the Mg+2 from blocking the site), Glycine present (will happen for activation of the receptor, so check). Say the NMDA receptor is now activated, releases Glutamate, blah blah blah, the Agmatine in the product in theory based on what I posted above is also endogenously released, so exogenous application will enhance that regulatory role of Agmatine so that in higher levels of NMDA receptor activation, it will inhibit the receptor from higher glutamate release (so overexcitation leading to potential neurotoxicity) by inhibting the receptor. Basically Agmatine might be able to prevent the neurotoxicity you always hear about when talking about DAA by preventing overexcitation of NMDA receptors/ reversing the levels of activation.

The other day neuron and you mentioned DAA as a nootropic on bb.com...how would you dose that for nootropic? Like if I get that flashover + DAA deal would it be best to take the two together perhaps preworkout (since flashover has glycine in it) and they would just work by building up in my system or does it work acutely like take it/them before I study/apply myself at work? My main goal would be taking it for increased mental performance since I was honestly going to throw the DAA in the traders thread before I read you guys talking about its nootropic potential